Consumer demand has recently spurred a proliferation of clear and colorless or "dye-free" products in the marketplace including, among others, liquid soaps, detergents and waxes, shampoos, hair sprays, cosmetics, deodorants, topical medications, beverages, parenteral alimentation solutions and orally ingestible pharmaceutical solutions. Consistent with this demand, the present invention proposes the use of propylene carbonate as a primary solvent in entirely anhydrous, clear and colorless composition bases or carriers systems for topical therapeutic and cosmetic preparations.
Many patent disclosures and other publications have described the use of propylene carbonate in pharmaceutical or cosmetic preparations. Additionally, some commercially available topically applied pharmaceuticals include propylene carbonate as a formulation constituent. For example, propylene carbonate has been used as a solvent in an ointment containing a topical steroid, fluocinolone acetonide (LIDEX.RTM.). U.S. Pat. No. 4,017,615 and Published European Patent Application 0 474 126 describe pharmaceutical ointment preparations. "Ointment" is generally defined in pharmaceutical science as a topical preparation containing medicament and petrolatum gel or fatty acids, as well as some cosolvents and penetration enhancers. Ointment has a greasy feel and is usually occlusive when applied to skin.
Other references, Published Japanese Patent Application Nos. 59-70612 and 59-190912, International Patent Publication Nos. WO 91/15210 and WO 94/13257, Published European Patent Specification 0 104 037 and U.S. Pat. No. 4,393,076, disclose topical gels, creams, lotions or solutions comprising water, propylene carbonate as a cosolvent and/or penetration enhancer, and other pharmaceutical excipients. Propylene carbonate is known to decompose in the presence of water into propylene glycol and carbon dioxide. However, carbon dioxide gas generation presents a physical stability problem inasmuch as a closed package tube containing the topical product may burst due to the pressure build-up from the accumulation of the carbon dioxide gas.
Propylene carbonate has also been disclosed for use in connection with film-forming formulations intended for therapeutic and cosmetic applications. For example, U.S. Pat. No. 4,963,591 discloses cosmetic compositions containing ethylcellulose as a film-forming agent and solvents including alcohol and propylene carbonate. The compositions form a curable, water-insoluble, occlusive film upon application to skin. And, European Patent No. 0 319 555 describes a pharmaceutical composition containing film-forming polymers, i.e., a vinylpyrrolidone-vinylacetate copolymer and polymethacrylic acid-butylester, and a mixture of solvents including propylene carbonate. This composition is also intended for transdermal therapeutic application, and will cure to form a flexible film when applied to skin. Regardless of the thinness, flexibility and other characteristics which are intended to enhance their appeal, many consumers nevertheless find such film-forming products to be uncomfortable and even unpleasant because of their occlusive nature.
Published European Patent Specification No. 0 271 332 discloses a composition saturated with a drug for forming a supersaturated composition when applied to a water-wetted area of human skin. This composition contains from 0.1 to 0.5% Klucel as anti-nucleating agent and a mixture of solvents including propylene carbonate, propylene glycol and ethanol. The composition thus requires supplemental water to perform its intended function. Further, it may also contain up to 50% water as a formulation constituent. Published European Patent Specification 0 272 045 describes a two-phase pharmaceutical composition for topical application. Prior to application, two parts must be mixed to form a composition containing a supersaturated drug. U.S. Pat. No. 4,820,724 discloses a dual phase solvent carrier system for topical drug application. The disclosed composition contains actives, a delivery solvent (e.g., benzyl alcohol, propylene carbonate, etc.) comprising about 5 to about 15 weight percent of the composition, and a fugitive solvent (e.g., various volatile alcohols) comprising about 75 to about 95 weight percent of the composition. U.S. Pat. No. 3,899,578 describes topical griseofulvin compositions comprising a solution, a gel, an anhydrous ointment, a paste or an emulsion of the drug in a solvent (e.g., benzyl alcohol, dimethyl phthalate, propylene carbonate and eugenol) and other pharmaceutical excipients. Published Japanese Patent Application No. 61-18716 discloses a tolnaftate gel produced by adding a powder of carboxyvinyl polymer gelation agent to and suspending it in a propylene carbonate solution of tolnaftate and any other medicinally active drugs. A lower alcohol such as ethanol or methanol is then added to dissolve the carboxyvinyl polymer. Then, a glycol (such as propylene, butylene, or hexylene glycol) and water are added. The glycol is believed to be added in order to assist in dissolution of the carboxyvinyl copolymer, thereby enhancing gelation of the composition. Lastly, an organic amine is added to neutralize the carboxyvinyl copolymer and gelation is effected.
A specific yet typical use contemplated by the composition base or "vehicle" formulations manufactured in accordance with the prior art as well as the present invention is as a carrier system for delivery of topical therapeutic products. For example, there are currently many topical antifungal products in the over-the-counter market which enable patients to self-treat athlete's foot, ringworm and jock itch. Although effective when properly used, most of these products require an application frequency of twice a day or more and 2 to 4 week treatment duration. Many persons find such continual attention to their treatment to be unduly burdensome. Consequently, many patients prematurely stop the treatment soon after the apparent symptom of itchiness has been alleviated. In this connection, it is believed that high relapse rates observed in patients suffering from these skin disease treatments are related to the noncompliance of patients to such cumbersome treatment regimens. A need exists, therefore, to develop more efficacious antifungal products which can reduce dosing frequency and/or treatment duration to assure a better therapeutic end result through increased treatment compliance.
A seemingly simple solution to patient compliance problems would be to increase the strength or dosage of the antifungal active ingredients in the formulation and thereby reduce application frequency. However, the use of more potent antifungal drugs is frequently not a viable approach. This is particularly true for patient self-directed treatments because of the potentiality for drug toxicity and other side effects such as skin irritation and sensitization. In self-applied topical therapeutic products, therefore, it would be much more desirable to employ antifungal drugs at conventional "over-the-counter" strengths in an improved carrier formulation to make drug delivery more efficacious. For example, the formulation should enhance the rate of drug penetration into the skin and mucosa tissues and prolong the drug retention in the fungus-residing superficial skin tissues, i.e., the stratum corneum and the epidermis in general. In addition, patient compliance with the treatment would be further promoted if such a product also would possess appealing cosmetic attributes and skin feel.